TGFβ1 Upregulates Expression of MMP-2 and MMP-9 through ERK Signaling Pathway in Gastric Carcinoma Cells

Objective To investigate the role of TGFβ1/ MAPK signaling pathways in the regulation of MMP-2 and MMP-9 in gastric carcinoma cells. Methods MKN45 and BGC823 gastric carcinoma cell lines were used in this study. The expression of MMP-2 and MMP-9 in the two gastric carcinoma cell lines stimulated by TGFβ1 was tested by Gelatin Zymography. The activity of MAPK signaling pathway in TGFβ1-stimulated cells was measured by Western blotting. The effects of the MAPK pathway specific inhibitors on TGFβ1-activated MMP-2 and MMP-9 expression in two cell lines were examined. Results TGF-β1 induced expression of MMP-2 and MMP-9 in MKN45 and BGC823 cells. P38 was activated in BGC823 cells by TGF-β, whereas NK and ERK was activated in both MKN45 and BGC823 cells. PD98059, a ERK specific inhibitor, significantly inhibited the production of MMP-2 and MMP-9 by TGF-β1 in both MKN45 and BGC823 cells, however, SB203580 and SP600125, specific blocker for P38 and JNK, showed no effect on the MMP-2 and MMP-9 expression in both two cells. Conclusion TGF-β1 induced enhanced MMP-2 and MMP-9 expression mediated by ERK signaling pathway in MKN45 and BGC823 gastric carcinoma cell lines.